Martin Castillo, BegoñaPernas, SòniaDorca i Sargatal, JordiÁlvarez, IsabelMartínez, SusanaPérez García, José ManuelBatista López, NorbertoRodríguez Sánchez, César A.Amillano, KepaDomínguez, SeverinaLuque, MariaStradella, AgostinaMorilla, IdoiaViñas, GemmaCortés, JavierCuyàs, ElisabetVerdura, SaraFernández-Ochoa, ÁlvaroFernández Arroyo, SalvadorSegura-Carretero, AntonioJoven, JorgePérez, ElsaBosch, Maria NeusGarcía, MargaritaLópez Bonet, EugeniSaidani, SamihaBuxó, MariaMenendez, Javier A.2021-06-222021-06-222018-11-021949-2553https://hdl.handle.net/2445/178654The METTEN study assessed the efficacy, tolerability, and safety of adding metformin to neoadjuvant chemotherapy plus trastuzumab in early HER2-positive breast cancer (BC). Women with primary, non-metastatic HER2-positive BC were randomized (1:1) to receive metformin (850 mg twice-daily) for 24 weeks concurrently with 12 cycles of weekly paclitaxel plus trastuzumab, followed by four cycles of 3-weekly FE75C plus trastuzumab (arm A), or equivalent regimen without metformin (arm B), followed by surgery. Primary endpoint was the rate of pathological complete response (pCR) in the per-protocol efficacy population. pCR rate was numerically higher in the metformin-containing arm A (19 of 29 patients [65.5%, 95% CI: 47.3-80.1]) than in arm B (17 of 29 patients [58.6%, 95% CI: 40.7-74.5]; OR 1.34 [95% CI: 0.46-3.89], P = 0.589). The rate of breast-conserving surgery was 79.3% and 58.6% in arm A and B (P = 0.089), respectively. Blood metformin concentrations (6.2 μmol/L, 95% CI: 3.6-8.8) were within the therapeutic range. Seventy-six percent of patients completed the metformin-containing regimen; 13% of patients in arm A dropped out because of metformin-related gastrointestinal symptoms. The most common adverse events (AEs) of grade ≥3 were neutropenia in both arms and diarrhea in arm A. None of the serious AEs was deemed to be metformin-related. Addition of anti-diabetic doses of metformin to a complex neoadjuvant regimen was well tolerated and safe. Because the study was underpowered relative to its primary endpoint, the efficacy data should be interpreted with caution.18 p.application/pdfengcc-by (c) Martin Castillo, Begoña et al., 2018https://creativecommons.org/licenses/by/4.0/Càncer de mamaMetforminaQuimioteràpiaBreast cancerMetforminChemotherapyinfo:eu-repo/semantics/article6857842021-06-22info:eu-repo/semantics/openAccess30479698